Lidamycin decreases CD133 expression in hepatocellular carcinoma via the Notch signaling pathway

Chen,Yi; Sun,Wenwei; He,Ran; Zhang,Feiyan; Wang,Hongyu; Li,Panhong; Shao,Rong‑Guang; Xu,Xiaoyu

doi:10.3892/ol.2017.7248

Lidamycin decreases CD133 expression in hepatocellular carcinoma via the Notch signaling pathway

Authors:
- Yi Chen
- Wenwei Sun
- Ran He
- Feiyan Zhang
- Hongyu Wang
- Panhong Li
- Rong‑Guang Shao
- Xiaoyu Xu
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Affiliations: College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, P.R. China, Laboratory of Oncology, Ministry of Health Key Laboratory of Antibiotic Bioengineering, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
Published online on: October 20, 2017 https://doi.org/10.3892/ol.2017.7248
Pages: 7889-7895

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Abstract

Cluster of differentiation (CD)133 is considered a molecular marker of cancer stem cells in hepatocellular carcinoma. In the present study, the effect of lidamycin (LDM) on CD133 expression in hepatocellular carcinoma (Huh7 cells) was evaluated and the potential molecular mechanism was investigated. Flow cytometry analysis, as well as sorting, sphere formation and western‑blot assays, were performed in vitro to explore the effects of LDM on CD133 expression. A subcutaneous tumor model in nude mice was used to observe the effects of LDM on tumor volume and CD133 protein in vivo. To investigate the potential underlying molecular mechanism, Notch signaling pathway activity was detected by western blot analysis and reverse transcription‑quantitative polymerase chain reaction. The proportion of CD133+ cells and the expression of CD133 protein were revealed to be downregulated by LDM. Sphere formation of sorted CD133+ cells was suppressed 7 days after LDM treatment. In addition, LDM inhibited tumor volume formed from sorted CD133+ cells and CD133 protein level in vivo. LDM decreased the mRNA level of NOTCH1, Hes1 (Hes family BHLH transcription factor 1) and Hey1 (Hes‑related family BHLH transcription factor with YRPW motif 1) genes; consequently, the protein expression of NOTCH1, Notch intracellular domain, Hes1 and Hey1 was decreased by LDM. Downregulation of the Notch signaling pathway by LDM was enhanced through combination with N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester. In brief, these data suggest that LDM suppresses CD133 expression via the Notch signaling pathway, indicating the potential mechanism of LDM on CD133 and the benefits for further clinical application.

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